SHY-867 is a pan-RAS inhibitor that effectively inhibits the binding of K-Ras protein and other members of the RAS small GTPase superfamily, with an IC50 value ranging from 0.5 to 3 μM. It effectively suppresses the phosphorylation of downstream targets such as MEK, ERK1/2, and AKT. Additionally, SHY-867 inhibits the formation of Ras-GTP active complexes and is applicable for research in pancreatic cancer and non-small cell lung cancer.

KRAS (WT):2 μM

SHY-867 competes with GTP for binding to K-Ras wild type, G12D, G12C, and Q61H mutants, as well as Rac-1, Rho-A, Rab5, and Rab35, with IC50 values of 2, 2.5, 1.2, 3, 2.5, 3, 0.5, and 0.75 μM, respectively. At concentrations of 0.1-1 μM for 72 hours, SHY-867 exhibits strong antiproliferative effects across various tumor cell lines, including pancreatic cancer (PANC-1, MIA PaCa-2, BxPC3) and non-small cell lung cancer (NCI-H1975, A549, NCI-H1299), with IC50 values ranging from 0.3 to 1 μM. Additionally, SHY-867 at 0.3-10 μM for 6 hours significantly inhibits EGF-induced phosphorylation of key signaling molecules in PANC-1, MIA PaCa-2, and NCI-H1975 cells. Moreover, at concentrations of 1.25-10 μM for 6 hours, SHY-867 impedes the formation of Ras-GTP complexes, showing IC50 values of 1-3 μM in PANC-1, MIA PaCa-2, and NCI-H1975 cells.